Propionate Metabolism in Mycobacterium Tuberculosis PDF Download
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Author: Suzana Anna Savvi
Publisher:
ISBN:
Category : Mycobacterium tuberculosis
Languages : en
Pages : 324
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Book Description
Author: Suzana Anna Savvi
Publisher:
ISBN:
Category : Mycobacterium tuberculosis
Languages : en
Pages : 324
Get Book Here
Book Description
Author: Wonsik Lee
Publisher:
ISBN:
Category :
Languages : en
Pages : 168
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Book Description
Mycobacterium tuberculosis is an air borne, facultative intracellular bacterial pathogen that resides in the phagosome of host cells. Virulence of M. tuberculosis is related to its abilities to respond to environmental cues encountered during infection and reprogram its metabolism to adapt to them. Nutrients derived from the host are key factors contributing to shape the carbon metabolism of M. tuberculosis during infection. This metabolic shift involves activation of fatty acid and cell wall lipids metabolism of the bacterium; however, the mechanistic interplay between them is undefined. In this study, to understand the metabolic adaptation on propionyl-CoA 3carbon product of cholesterol in M. tuberculosis, the propionate detoxification and methyl-branched (MB) lipid synthesis pathways were investigated. The data presented here shows that excess propionyl-CoA was toxic to M. tuberculosis, as the propionylCoA inhibited pyruvate dehydrogenase (PDH) and acetate or fatty acid rescued the toxicity through providing acetyl-CoA the product of PDH. A mechanistic insight was revealed by metabolic labeling with radioactive propionate and fatty acids: the given fatty acids facilitate propionyl-CoA incorporation into a key MB lipid PDIM by serving as acyl-primers required for its biosynthesis. Additionally, to further define genes required for propionate and fatty acid metabolism an approach exploiting propionate toxicity and TraSH analysis was employed. The data from the genetic profiling by TraSH confirms our model for the fatty acids rescue from the propionate toxicity and suggests putative roles for uncharacterized genes in MB lipids synthesis and fatty acid metabolism. This model was also validated by using lipid droplet loaded macrophage where M. tuberculosis exploited fatty acids from the host lipid droplet to synthesis PDIM resulting in reduction of the propionate stress. Data presented in this work demonstrates that the propionyl-CoA processing is a significant problem for survival in the host cell, and that the routing of propionyl-CoA into MB cell wall lipids plays an important role for limiting the metabolic stress derived from propionate. And, the data also demonstrates that the fatty acids from lipid droplets in the host macrophage may provide a well-balanced diet that retains appropriate level of acetyl-CoA and propionyl-CoA.
Author: Christopher James Rocco
Publisher:
ISBN:
Category :
Languages : en
Pages : 226
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Book Description
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 23
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Book Description
Background: Because metabolism is fundamental in sustaining microbial life, drugs that target pathogen-specific metabolic enzymes and pathways can be very effective. In particular, the metabolic challenges faced by intracellular pathogens, such as Mycobacterium tuberculosis, residing in the infected host provide novel opportunities for therapeutic intervention. Results: We developed a mathematical framework to simulate the effects on the growth of a pathogen when enzymes in its metabolic pathways are inhibited. Combining detailed models of enzyme kinetics, a complete metabolic network description as modeled by flux balance analysis, and a dynamic cell population growth model, we quantitatively modeled and predicted the dose-response of the 3-nitropropionate inhibitor on the growth of M. tuberculosis in a medium whose carbon source was restricted to fatty acids, and that of the 5'-O-(N-salicylsulfamoyl) adenosine inhibitor in a medium with low-iron concentration. Conclusion: The predicted results quantitatively reproduced the experimentally measured dose-response curves, ranging over three orders of magnitude in inhibitor concentration. Thus, by allowing for detailed specifications of the underlying enzymatic kinetics, metabolic reactions/ constraints, and growth media, our model captured the essential chemical and biological factors that determine the effects of drug inhibition on in vitro growth of M. tuberculosis cells.
Author: Suzie Hingley-Wilson
Publisher: Frontiers Media SA
ISBN: 2832519164
Category : Medical
Languages : en
Pages : 297
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Book Description
The macrophage (or “big eater”) is often considered the first cell type to encounter the causative agent of Tuberculosis (TB), Mycobacterium tuberculosis, upon entry to the lung. Once inside the macrophage the tubercle bacillus can survive and even replicate where many other invading pathogens perish. Recent research suggests the bacilli adapts within this hostile environment, treating the macrophage like a Trojan horse. Indeed, cutting-edge techniques have revealed that the degree of bacterial heterogeneity and resistance to antibiotics changes within the macrophage. M. tuberculosis spends most of its life cycle within the macrophage and has adopted specific mechanisms to survive, egress and to recruit more of this niche cell (eg the Type VII secretion system ESX-1). Understanding the host-pathogen interaction in tuberculous infection is key to understanding TB, which remains the number one cause of death from a bacterial infection. In this research topic we aim to cover advances in understanding how the tubercle bacillus adapts and survives within the host cell. Determining the responsible mechanisms may reveal novel ways to target this deadly pathogen and halt its adaptation and transformation within these potentially destructive or permissive cells.
Author: Tyrrell Conway
Publisher: John Wiley & Sons
ISBN: 1555818889
Category : Science
Languages : en
Pages : 382
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Book Description
Groundbreaking thinking on how bacterial metabolism is foundational to pathogenesis For too long, bacterial metabolism and bacterial pathogenesis have been studied as separate entities. However, the scientific community is beginning to realize that not only are bacterial nutrient acquisition and utilization essential for pathogenesis, but that interfering with the pathogen-specific metabolic pathways used during infection can regulate virulence factor expression and might lead to effective breakthroughs in a variety of treatments. Editors Paul Cohen and Tyrrell Conway, who pioneered the use of metabolic mutants in competitive colonization assays, an approach now widely used to investigate the nutrition of pathogens in vivo, are uniquely qualified to advance our knowledge of this integrative field of research. They convened a group of contributors who are breaking new ground in understanding how bacterial metabolism is foundational to pathogenesis to share their expert perspectives and outlook for the future. Beginning with overviews, Metabolism and Bacterial Pathogenesis covers a wide range of diseases and both Gram-positive and -negative bacteria that serve as model systems for in vitro and in vivo investigations intracellular, respiratory, and enteric pathogens pathogen-specific nutrient acquisition in hosts mechanisms of host-driven metabolic adaptation by pathogens metabolic regulation of virulence gene expression Useful for specialists in bacterial pathogenesis and specialists in metabolism as well as molecular biologists, physicians, veterinarians, dentists, graduate and undergraduate students, and laboratory technicians, Metabolism and Bacterial Pathogenesis is also essential reading for scientists studying the microbiome.
Author: Mamadou Daffé
Publisher:
ISBN: 9781555814687
Category : Bacterial cell walls
Languages : en
Pages : 0
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Book Description
Explains the unique characteristics that cause this large group of bacteria responsible for tuberculosis and leprosy to function differently; serves as a valuable reference for those working in the areas of biochemistry, genetics, genomics, and immunology.
Author: William R. Jacobs, Jr.
Publisher: John Wiley & Sons
ISBN: 1555819567
Category : Medical
Languages : en
Pages : 741
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Book Description
Can today's innovative practices and molecular tools tame this ancient disease? One third of the world's population is infected with tuberculosis (TB), with about 10 million new cases annually. To combat TB and its agent, Mycobacterium tuberculosis, the World Health Organization launched The End TB Strategy, which aims to slash the suffering and cost of TB by 2035. This makes the second edition of Tuberculosis and the Tubercle Bacillus, edited by Jacobs, McShane, Mizrahi, and Orme, an extremely valuable resource for scientists and clinicians. The editors have gathered their colleagues from around the world to present the latest on the molecular biology of M. tuberculosis and related species, the host-pathogen interactions that enable invasion, and the host's immune response to M. tuberculosis infection. The basic, clinical, and translational research presented in this book supports the goals of WHO's End TB Strategy by driving toward the development of effective vaccines, rapid molecular diagnostics, and anti-TB drugs. Creating an effective tuberculosis vaccine. Understand the innate and adaptive immune response to M. tuberculosis infection, its study in established animal models, and how this information is being used to develop new vaccines against TB. Formulating new antituberculosis drugs. Learn the challenges and methods for evaluating new drugs in preclinical trials with a focus on drugs that work against "persisters" and those that act on the electron transport complex and ATP synthase of M. tuberculosis. Overcoming the challenges of diagnosing tuberculosis. Review new diagnostic tools that are simple, rapid, affordable, specific, sensitive, and safe, including molecular-based diagnostic methods such as GeneXpert MTB/RIF. Using molecular, genomic, and bioinformatics tools to understand the biology and evolution of Mycobacterium. Explore current research on the molecular mechanisms that M. tuberculosis uses to evade the immune system, enter a state of nonreplicating persistence, and become reactivated. The second edition of Tuberculosis and the Tubercle Bacillus presents the latest research on a microorganism that is exquisitely well adapted to its human host. This pathogen continues to confound scientists, clinicians, and public health specialists, who will all find much valuable information in this comprehensive set of reviews.
Author: Rodrigo Valenzuela Baez
Publisher: BoD – Books on Demand
ISBN: 9535109448
Category : Medical
Languages : en
Pages : 476
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Book Description
Lipids (fats and oils) are a wide range of organic molecules that serve several functions in organisms. Lipids are essential components of our diet, highlighting their important contribution in energy, representing 9 kcal/g (or 37.7 kJ/g), and by some components relevant to the metabolism, such as essential fatty acids, fat soluble vitamins and sterols (cholesterol and phytosterols). Besides this, lipids have key roles in human growth and development, along with promoting, preventing and/or participating in the origin or eventually in the treatment of various diseases. This book presents a systematic and comprehensive review about the structure and metabolism of lipids, particularly highlighting the importance of these molecules in the body and considering the interest of some lipids in health and disease.
Author: Indira T. Kudva
Publisher: John Wiley & Sons
ISBN: 1555819281
Category : Medical
Languages : en
Pages : 871
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Book Description
Ground-breaking overview of an enduring topic Despite the use of antibiotics, bacterial diseases continue to be a critical issue in public health, and bacterial pathogenesis remains a tantalizing problem for research microbiologists. This new edition of Virulence Mechanisms of Bacterial Pathogens broadly covers the knowledge base surrounding this topic and presents recently unraveled bacterial virulence strategies and cutting-edge therapies. A team of editors, led by USDA scientist Indira Kudva, compiled perspectives from experts to explain the wide variety of mechanisms through which bacterial pathogens cause disease: the host interface, host cell enslavement, and bacterial communication, secretion, defenses, and persistence. A collection of reviews on targeted therapies rounds out the seven sections of this unique book. The new edition provides insights into some of the most recent advances in the area of bacterial pathogenesis, including how metabolism shapes the host-pathogen interface interactions across species and genera mechanisms of the secretion systems evasion, survival, and persistence mechanisms new therapies targeting various adaptive and virulence mechanisms of bacterial pathogens Written to promote discussion, extrapolation, exploration, and multidimensional thinking, Virulence Mechanisms of Bacterial Pathogens serves as a textbook for graduate courses on bacterial pathogenesis and a resource for specialists in bacterial pathogenicity, such as molecular biologists, physician scientists, infectious disease clinicians, dental scientists, veterinarians, molecular biologists, industry researchers, and technicians.
